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血管相关平滑肌细胞蛋白(VASN)通过Yes相关蛋白(YAP)/具有PDZ结合基序的转录共激活因子(TAZ)轴促进前列腺癌的增殖。

VASN promotes proliferation of prostate cancer through the YAP/TAZ axis.

作者信息

Cui F-L, Mahmud A-N, Xu Z-P, Wang Z-Y, Hu J-P

机构信息

Department of Urology Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6589-6596. doi: 10.26355/eurrev_202006_21644.

DOI:10.26355/eurrev_202006_21644
PMID:32633347
Abstract

OBJECTIVE

The purpose of this study was to uncover the role of VASN in regulating proliferative ability of prostate cancer (PCa) cells through the yes-associated protein/transcriptional coactivator with PDZ-binding motif (YAP/TAZ) axis, thus influencing the progression of PCa.

PATIENTS AND METHODS

VASN, YAP, and TAZ levels in PCa tissues or in the serum were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The diagnostic value of VASN in PCa was assessed by introducing receiver operating characteristic (ROC) curves. Besides, the regulatory effects of VASN on viability, clonality, and expression levels of YAP/TAZ were evaluated by cell counting kit-8 (CCK-8), colony formation, and Western blot, respectively. Finally, rescue experiments were conducted to uncover the involvement of YAP in VASN-regulated proliferation of PCa.

RESULTS

Results manifested that VASN, YA, and TAZ were upregulated in PCa patients, and VASN presented a certain diagnostic value. Knockdown of VASN in LNCaP and C4-2 cells suppressed viability and clonality, and downregulated protein levels of YAP and TAZ. Notably, overexpression of YAP abolished the attenuated viability and clonality in PCa cells with VASN knockdown.

CONCLUSIONS

VASN promotes proliferative ability in PCa via regulating the YAP/TAZ axis, thus aggravating the progression of the disease.

摘要

目的

本研究旨在揭示血管粘附分子(VASN)通过Yes相关蛋白/含PDZ结合基序的转录共激活因子(YAP/TAZ)轴调节前列腺癌细胞增殖能力的作用,从而影响前列腺癌的进展。

患者与方法

采用定量实时聚合酶链反应(qRT-PCR)检测前列腺癌组织或血清中VASN、YAP和TAZ的水平。通过绘制受试者工作特征(ROC)曲线评估VASN在前列腺癌中的诊断价值。此外,分别采用细胞计数试剂盒-8(CCK-8)、集落形成实验和蛋白质免疫印迹法评估VASN对细胞活力、克隆形成能力以及YAP/TAZ表达水平的调节作用。最后,进行挽救实验以揭示YAP在VASN调节的前列腺癌增殖中的作用。

结果

结果表明,前列腺癌患者中VASN、YAP和TAZ表达上调,且VASN具有一定的诊断价值。在LNCaP和C4-2细胞中敲低VASN可抑制细胞活力和克隆形成能力,并下调YAP和TAZ的蛋白水平。值得注意的是,YAP的过表达消除了VASN敲低的前列腺癌细胞中减弱的细胞活力和克隆形成能力。

结论

VASN通过调节YAP/TAZ轴促进前列腺癌的增殖能力,从而加剧疾病进展。

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